Long non-coding RNA Xist contribution in systemic lupus erythematosus and rheumatoid arthritis

• Published in: Clinical immunology (Orlando, Fla.) Vol. 236; p. 108937
• Main Authors: Bost, Chloé, Arleevskaya, Marina I., Brooks, Wesley H., Plaza, Samuel, Guery, Jean-Charles, Renaudineau, Yves
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.03.2022; Elsevier
• Subjects: Arthritis, Rheumatoid - genetics; Arthritis, Rheumatoid - metabolism; Female; Humans; Immunology; Interferon pathway; Life Sciences; Long non-coding RNA Xist; Lupus Erythematosus, Systemic - genetics; Lupus Erythematosus, Systemic - metabolism; MicroRNAs - genetics; Rheumatoid arthritis; RNA, Long Noncoding - genetics; RNA, Long Noncoding - metabolism; Synoviocytes - metabolism; Systemic lupus erythematosus; X chromosome; Systemic lupus erythematosus; Long non-coding RNA Xist; Rheumatoid arthritis; X chromosome; Interferon pathway
• ISSN: 1521-6616; 1521-7035; 1521-7035
• DOI: 10.1016/j.clim.2022.108937

Growing evidence points towards the role of the long non-coding (lnc)-RNA Xist expressed in female cells as a predominant key actor for the sex bias observed in systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). Indeed, in female cells, lnc-Xist controls transcription directly by spreading across the inactivated X chromosome (Xi) and indirectly by sequestring miRNAs as a sponge. The inactivation process at Xi is altered in lymphocytes from SLE women and associated with important variations in ribonucleoproteins (RNP) associated with lnc-Xist. In fibroblast-like synoviocytes (FLS) and osteoclasts from RA women, proinflammatory and proliferative pathways are upregulated due to the sequestration effect exerted by lnc-Xist overexpression on miRNAs. The key role played by lnc-Xist in SLE and RA is further supported by it's knock down that recapitulates the SLE B cell extrafollicular profile and controls RA associated FLS proinflammatory cytokine production and proliferation. •Lnc-Xist controls X chromosome inactivation and miRNAs in females.•Lnc-Xist and RNP expression are dysregulated in autoimmune diseases.•Lnc-Xist dependent type I interferon and extrafollicular B cell pathways are defective in SLE.•Fibroblast-like synoviocyte (FLS) capacities in RA are controlled by lnc-Xist.